Tissue oximetry apparatus and method

ABSTRACT

An apparatus and method for determining tissue oxygenation such as arterial and venous oxygenation and cerebral oxygenation. In one embodiment, the optical properties of tissue are determined using measured light attenuations at a set of wavelengths. By choosing distinct wavelengths and using light attenuation information, the influence of variables such as light scattering, absorption and other optical tissue properties can be minimized.

RELATED APPLICATIONS

This application is a continuation of and claims the benefit of priorityunder 35 U.S.C. §120 to U.S. patent application Ser. No. 13/283,044,filed on Oct. 27, 2011, which is a continuation of and claims thebenefit of priority under 35 U.S.C. §120 to U.S. patent application Ser.No. 11/780,997, filed on Jul. 20, 2007, which is a continuation-in-partof and claims the benefit of priority under 35 U.S.C. §120 to U.S.patent application Ser. No. 11/078,399 filed on Mar. 14, 2005, each ofwhich applications is incorporated by reference herein in its entirety.

TECHNICAL FIELD

The present invention relates to a process and apparatus for improvingaccuracy of optical measurements of oxygenation of blood in tissue.

BACKGROUND OF THE INVENTION

A standard method to measure the arterial oxygenation of blood is knownas pulse oximetry. Pulse oximeters function on the basis that atdiffering wavelengths, blood attenuates light very differently dependingupon the level of oxygenation. Pulse waves starting from the heart causein the arterial blood vessel system a periodic fluctuation in thearterial blood content in the tissue. As a consequence, a periodicchange in the light absorption (FIG. 1) can be registered between thelight transmitter, whose radiation passes through the tissue, and thereceivers, which are integrated in a pulse oximetry sensor. Theevaluation of the sensor signals is normally carried out at lightwavelengths of w1=660 and w2=940 nm by calculating the differentialchange of light absorption. It is possible to create a measured variableR which is obtained in the following manner or in a similar manner:

$\begin{matrix}{{R = {{Rw}\; 1}},{{w\; 2} = \frac{{\Delta \left( {{LAw}\; 1} \right)} = {{\ln \left( {{I\; \max},{w\; 1}} \right)} - {\ln \left( {{I\; \min},{w\; 1}} \right)}}}{{{\Delta \left( {{LAw}\; 2} \right)}\mspace{31mu} {\ln \left( {{I\; \max},{w\; 2}} \right)}} - {\ln \left( {{I\; \min},{w\; 2}} \right)}}}} & {{Eq}\text{:}\mspace{14mu} (1)}\end{matrix}$

The light intensities described in the formula represent the lightintensities received in the receiver of the sensors used in pulseoximetry. The measured variable R serves as a measurement for the oxygensaturation. The formation of a quotient in order to form the measuredvariable is intended to compensate for any possible influences thehaemoglobin content of the tissue, the pigmentation of the skin or thepillosity may have on the measurement of the oxygen saturation ofarterial blood. The difference of the light attenuations at a minimumand maximum value is the delta of the light attenuations for each ofboth wavelengths.

Measuring oxygen saturation of arterial blood in the tissue in a rangeof 70 to 100% using light of wavelength 940 nm and 660 nm most oftenproduces for one single application site sufficiently accurate measuredvalues. However, in order to measure lower oxygen saturation of arterialblood it is necessary to assume a strong influence on the measuredvariable lit in particular caused by perfusion (i.e. blood content)(see: IEEE; Photon Diffusion Analysis of the Effects of MultipleScattering on Pulse Oximetry by J. M. Schmitt; 1991) and other opticalparameters of tissue.

U.S. Pat. No. 5,529,064 to Rall, describes a fetal pulse oximetrysensor. For this kind of application, a higher measurement precision isdesirable because a fetus has a physiological lower oxygenation thanadult human beings and measurement error of SaO2 increases at lowoxygenations.

U.S. Pat. No. 6,226,540 to Bemreuter, incorporated by reference herein,improves the precision of pulse oximetry, However, in order to measureon different body sites with the same high resolution for the arterialoxygenation, additional precision to measure optical tissue propertiesis necessary. Another problem is that pulse oximetry alone does notprovide sufficient diagnostic information to monitor critically illpatients (See: When Pulse Oximetry Monitoring of the Critically Ill isNot Enough by Brian F. Keogh in Anesth Analg (2002), 94:96-99).

Because of this it would be highly desirable to be able to additionallymeasure the mixed venous oxygenation of blood SvO2. Methods to measureSvO2 with NIR were described by Jöbsis in U.S. Pat. No. 4,223,680 and byHirano et al in U.S. Pat. No. 5,057,695. A problem of those disclosedsolutions is that hair, dirt or other optically non-transparent materialon the surface of tissue can influence the measured results for SvO2.

To measure the metabolism of blood oxygenation, Anderson et al in U.S.Pat. No. 5,879,294 disclose an instrument in which the second derivativeof the light spectrum used delivers information about the oxygenation.Hereby, the influence of light scattering in tissue is minimized, whichcan result in higher measurement precision. A disadvantage of thissolution is that the calibration of the optical instruments iscomplicated and expensive, which makes it impractical to use suchdevices for sports activity applications, where light weight wearabledevices would be of interest. Similar problems are known for frequencydomain spectroscopy disclosed for example in Grafton, U.S. Pat. No.4,840,485. Oximetry devices, which are described in the presentspecification and which simply measure light attenuations of tissue atdifferent wavelengths, are more feasible, flexible and reliable inpractice than complex time resolved methods.

BRIEF SUMMARY OF THE INVENTION

The present invention is directed to an apparatus and method whicheliminate influences on calibration by subtracting and adding measuredlight attenuations, and a model-based calibration calculation to improveprecision of measured output variables. In one embodiment, an apparatusutilizes a combination of light emitters and detectors with a lightwavelength combination of more than two wavelengths, where the peakspectrum of a third wavelength is about the geometric mean value of thefirst and second wavelengths.

As a result, influences on the calibration of different tissueproperties can be minimized in order to measure arterial or venous orthe combination of arterial and venous oxygenation. It has beendiscovered that by choosing one of the wavelengths as a geometric meanvalue of two other wavelengths, variations due to scattering can bereduced. Additional determination of light attenuation can reducemeasurement errors because of variations of light absorption due todifferent tissue composition, i.e., variations of relative amounts ofmuscle, skin, fat, bone, etc.

The foregoing has outlined rather broadly the features and technicaladvantages of the present invention in order that the detaileddescription of the invention that follows may be better understood.Additional features and advantages of the invention will be describedhereinafter which form the subject of the claims of the invention. itshould be appreciated by those skilled in the art that the conceptionand specific embodiment disclosed may be readily utilized as a basis formodifying or designing other structures for carrying out the samepurposes of the present invention. It should also be realized by thoseskilled in the art that such equivalent constructions do not depart fromthe spirit and scope of the invention as set forth in the appendedclaims. The novel features which are believed to be characteristic ofthe invention, both as to its organization and method of operation,together with further objects and advantages will be better understoodfrom the following description when considered in connection with theaccompanying figures. It is to be expressly understood, however, thateach of the figures is provided for the purpose of illustration anddescription only and is not intended as a definition of the limits ofthe present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the present invention, reference isnow made to the following descriptions taken in conjunction with theaccompanying drawing, in which:

FIG. 1 is a graph showing changes of light absorption by blood overtime;

FIG. 2 is a graph illustrating the dependency of arterial oxygensaturation on the measurement variable R for different optical tissueproperties;

FIG. 3 shows a reflectance oximetry sensor according to the invention inschematic cross-section;

FIG. 4 shows a finger clip sensor according to the invention inschematic cross-section;

FIG. 5 is a diagram of a multidimensional calibration of oxygenation forthe two measuring variables R1, R2 vs SaO2;

FIG. 6 is a schematic diagram of an oximetry system in operation;

FIG. 7 is a side view of a fetal scalp sensor according to theinvention;

FIG. 8 is a bottom view of the sensor of FIG. 7;

FIG. 9 is a bottom view of the sensor of FIG. 3;

FIG. 10 is a side cross-sectional view of a variation of the sensor ofFIG. 3;

FIG. 11 is a side cross-sectional view of another variation of thesensor of FIG. 3;

FIG. 12, FIG. 12A-12D is a bottom view of the sensor of Figure Handseveral variations of emitter detector position on sensor interface;

FIGS. 13A, 13B and 14 are side cross-sectional views of reflectancesensors fixed on the forehead;

FIG. 15 shows a system for determining cardiac output;

FIG. 16 shows person with wrist worn display and sensor interface withsensor applications on different sites of the body, two sensorinterfaces for each hemnisphere of brain placed on the forehead;

FIG. 17A is a schematic diagram of a hardware processing unit for anoximetry system according to the invention with detector ground shieldand elastic isolating layer towards tissue, and FIG. 17B includes a sideview of a sensor part;

FIG. 18 is a diagram of a multidimensional calibration of oxygenationfor the two measuring variables Rv1, Rv2 vs. SvO2; and

FIG. 19 is a flow chart illustrating signal processing flow for amodel-based determination of oxygen in blood.

DETAILED DESCRIPTION OF TELE INVENTION

It is noted that as used in the present specification, “venous” and“mixed venous” may be synonyms, “attenuation” may refer to absolute ordifferential attenuation, “tissue oxygenation” may refer to arterial,mixed venous, or venous oxygenation or a combination of thereof, and thephrase “about” in reference to wavelengths may quantify in a band of+/−80 nm and in reference to distances quantifies in a band of +/−1 cmand that emitter corresponds to emitting point that means an area wherelight of at least one wavelength emitted by the sensor interface startspenetrating tissue, weighted values for light attenuations can have avalue of one ore different values, the pulsatile part of a lightattenuation corresponds to the AC signal of pulse oximetry and thenon-pulsating part to the DC signal.

The diagram of FIG. 1 shows the fundamental effect on which pulseoximetry and comparable methods to determine arterial blood oxygenationare based. When measuring light absorption of tissue in vivo lightabsorption changes synchronously with every heart cycle. The diagramillustrates the change of light absorption versus time, which is causedby arterial pulsations that can be measured while systole and diastole.During systole and diastole the pressure on the arterial vessel systemvaries from 80 mmHg to 120 mmHg. The change of light absorption iscalled the AC-signal. The DC-signal, the time-invariant part of lightabsorption, is caused by the non-pulsating part of the arterial blood,the venous blood, bone, hair, tissue and other constant absorbingconstituents versus time. The time-invariant signal is the basis for thecalculation of the mixed venous oxygenation of tissue; thus, a majorpart of the absorption is caused by venous blood and a minor part byarterial blood.

FIG. 2 shows two calibration curves in a diagram with SaO2 vs. R.Calibration line 42 is only valid for a first distinct set of opticalproperties. Calibration line 40 is only valid for a second distinct setof optical properties. The valid set of optical properties can bedetermined by an optical system illustrated in FIGS. 3 and 6 with asensor 31S, which is placed on tissue 46 and connected via a plug 66 toa display device 64. Additionally, FIG. 2 shows two horizontal lines atSaO2=0.6 and at SaO2=0.4 and one vertical line at R=1.4. If an opticalsystem determines only R without registering the two different sets ofoptical properties, this would result in an error of 0.2 SaO2 (SaO2 atfirst set of optical properties—SaO2 at second set of opticalproperties). An analogous relation also exists for the mixed venoussaturation of blood SvO2 and a measurement variable Rv1 and Rv2 formixed venous oxygenation (FIG. 18).

FIG. 3 shows an oximetry sensor 31S on the upper part of the figurewhich is placed on tissue 46. The sensor 31S contains two light emitters31E, 32E and two light detectors 31D, 32D. The arrows A1 through A4 showhow light passes from emitters to detectors through tissue. A1 standsrepresentative for light which is emitted in emitter 31E and received indetector 31D. A2 is light emitted in emitter 32E and detected indetector 31D. A3 is light emitted in 31E and received in 32D and A4 islight emitted in emitter 32E and detected in detector 32D.

FIG. 4 shows a finger clip sensor 54 which is fixed on a finger 48. Thefinger clip sensor incorporates emitters 31E, 32E and detectors 31D,32D. The electrical sensor signals of the finger clip sensor aretransmitted via a sensor cable 60. The signals can also be convenientlytransmitted wirelessly by means well known in the art (not shown).

FIG. 5 illustrates a multidimensional calibration of SaO2 vs. R1 and R2.A certain combination of R1 and R2 corresponds to a data point on thecalibration plane, which indicates the saturation level SaO2. Ananalogous relation also exists in FIG. 18 for the mixed venoussaturation of blood SvO2 and two related measurement variables Rv1 andRv2 for mixed venous oxygenation.

FIGS. 7 and 8 show a fetal scalp sensor 74 with a set of emitters 31E,32E, 33E and 34E and a set of detectors 31D, 32D, 33D and 34D from sideand bottom views, respectively. The sensor can be fixed on the scalp ofthe fetus via a spiral needle 76 during labor. Additionally, anelectrocardiogram (ECG) of the fetus can be transmitted via the needle76.

FIG. 9 is a bottom view of sensor 31S from FIG. 3. Detectors 35D and 36Dhave a concentric form to maximize reception of light emitted by theemitters 31E and 32E.

FIGS. 10-12 show several modifications of sensor 31S. FIG. 10 showssensor in side view with a flat body where detectors 31D, 32D and theemitter 32D are grouped close together and emitter 32E is positioned farfrom this group. The sensor can be fixed via a band 108 on tissue. Alight shield 110 minimizes the influence of ambient light.

FIG. 11 shows a sensor with a sensor holder 22.

FIG. 12 is a bottom view of sensor of FIG. 11. The bottom side of sensorholder 122 can be covered with medical glue or adhesive. If sensorholder 122 is placed on sensor 31S according to FIG. 11 and applied totissue 46, fixation is possible by glue on sensor holder 122. Sensorholder 122 can be constructed as inexpensive and disposable.Alternatively, the bottom side of the sensor, which is applied totissue, can be directly covered with glue. The disadvantage of this isthat the sensor can not be reused. The heart rate is detected viaECG-electrode 123 which contacts the skin, FIG. 12A shows a sensor wherethe emitters 31E and 132E are placed close and a first detector 31D1 ispositioned near and a second 32D is positioned far towards the emitters,FIG. 12B is a slight modification of FIG. 12B showing a sensor wheredetector 31D1 is positioned in one line with the emitters 31E and 132E.In FIG. 12C instead of detector 31D1 two detectors 31D1 and 31D2 areillustrated. FIG. 12D is a modification of FIG. 12C showing thatdetectors 31D1 and 31D2 can be placed in various topologies on thesensor interface here close to the emitters 31E and 132E.

FIGS. 13A, 13B and 14 show variations of sensor 32S applied on theforehead of a person. In the first variation shown in FIG. 13A and 13B,sensor 32S is fixed via a band 108 to the forehead. The arrows A32 andA42, which represent how light travels from the emitters 31E, 32E to thedetectors 31 and 32D, pass through forehead tissue 152 and bone of skull150 and pass or touch brain 148. The arrows A12 and A22 only passthrough forehead tissue 152 and bone of skull 150. A difference of FIG.13A and FIG. 13B is that in FIG. 13A the detectors 31D and 32D arepositioned in close proximity whereas in FIG. 13B the emitters areplaced in close proximity.

The second variation of sensor 32S also applied on the forehead is shownin FIG. 14. The arrows A11, A21, A31 and A41 compared with arrows A12,A22, A32 and A42 of FIGS. 13A and 13B show that by variation of theposition of light detectors and emitters, oxygen content can be senseddifferently without changing the outline of the sensor variation used.

FIG. 15 shows a patient lying on a bed being supplied with oxygen by anintubation tube 210, and an anesthesia machine 204. The anesthesiamachine 204 is connected to the patient and has an inventive device formeasuring oxygen consumption or carbon dioxide production of thepatient. The sensor 32S is placed on the forehead of the patient, and isconnected with oxygen extraction monitoring device 206, which calculatesSaO2 and SvO2 and oxygen extraction. The monitoring device 206 and theanesthesia machine 204 are linked to a third device 202, whichcalculates cardiac output or trend of cardiac output.

FIG. 16 illustrates the use of oxygen monitoring at differentapplication sites e.g. for sports activity or other medicalapplications, in which a wrist worn display device 220 can receiveoxygenation data from a forehead-band-sensor with sensor interfaces 214and 215 for both hemispheres of brain, from a chest-band-sensor 224,from an arm-band-sensor 218 or a special variation of this the wristband with sensor interface 221 or from a finger-glove-sensor 222.

FIG. 17a shows the hardware for evaluating oxygenation by using twoemitters 31E and 32E and two detectors 31D and 32D. The LED-drive 226energizes the two emitters via lines 238, 248 which can incorporatecoding hardware, to adjust calibration for the multidimensionalcalibration or to adjust calibration for varying emitter detectorgeometry. The amplifiers AMP1 232 and AMP2 234 are connected todetectors 31D and 32D. The demultiplexer DEMUX 230 selects eachwavelength used in every emitter timed synchronously according to theswitching state of the LED-DRIVE 226 and delivers the measured data viaan AD-Converter AD-CONV 236 to the CPU 228. The sensor interfacescomprises an isolating layer 239 towards the patient which may consistof elastic material. The light detectors 31D and 32D are shielded with agrounded layer 233 which is connected to a ground line 235. The groundshield can consist for example of an electrical conductive layer ormetallic grid. FIG. 17b depicts a cross-sectional view of sensor 240.

FIG. 19 illustrates the signal flow of a model-based calibration. Aninput processing circuit 260 is the first part of the signal flow. Theprocessing circuit is connected with a circuit for calculating lightattenuations 262 and a circuit calculating different measurementvariables 264. The calculation for light attenuations 262 is a basis fora model-based determination circuit for mixed venous oxygenation 266with a joint circuit to output a value for the mixed venous oxygenationSvO2 270. A model-based determination circuit for arterial oxygenation268 is connected to the circuit for calculating light attenuations 262and the circuit calculating different measurement variables 264, Theoutput value for a arterial oxygenation circuit for SaO2 272 is linkedto the model-based calculation for SaO2 268.

By using three instead of two wavelengths to measure the arterialoxygenation, the following approximation can be derived with the help ofdiffusion theory. The result of this operation is:

$\begin{matrix}{R^{\prime} = \frac{{{Rw}\; 2},{{w\; 1*{LAw}\; 2*{LAw}\; 0} + Q}}{{{Rw}\; 1},{w\; 0\mspace{31mu} {LAw}\; 1*{LAw}\; 1}}} & {{eq}.\mspace{11mu} (2)}\end{matrix}$

where Rw2,w1 and Rw1,w0 are calculated according to equation) usingwavelengths w0, w1, and w2 and Q is a correction parameter.

Light attenuation LAwx can be calculated in the following or similarmanner:

LAwx=In(Iwx/Iwxo)   eq. (3)

LAwx corresponds to the logarithm of the ratio of light intensity Iwxowhich is the emitted and light intensity Iwx the received light passingthrough tissue at wavelength wx. The index following suffix wx indicatesthe selected wavelength. Graaff et al showed that scattering in tissuedecreases for higher wavelengths according to exponential functions(see: Applied Optics; Reduced Light-Scattering Properties for Mixturesof Spherical Particles: A Simple Approximation Derived from MieCalculations by R. (Graaff, 1992).

Absorption variation may also be taken from other measures orapproximations such as the ac/dc ratio. The amplitude may be any measuresuch as peak-to-peak, RMS, average, or cross correlation coefficient, Itmay also be derived from other techniques such as Kalman filtering or ameasure of the time derivative of the signal. Also, while calculationsutilizing ratios of absorptions at different wavelengths are shown,alternate calculations may be used to give the same or approximately thesame results. For instance the absorptions could be used directly,without calculating the ratios.

A preferred selection of the wavelengths combination to reduce theinfluence of scattering is defined by the following equation, withwavelength with as the geometrical mean value of wavelength w0 andwavelength w2, defined as:

w1=SQRT(w0*w2)   eq. (4)

This combination minimizes the variation band of correction parameter Q,which has a default value of about one. The measurement variable ofequation (2) has minimized error related to variation of scattering andblood content of tissue.

EXAMPLE 1

The sensor 31S shown in FIG. 3 is used to determine the arterialoxygenation and the mixed venous blood oxygenation of tissue withimproved precision. Equation (2) is used to provide a measurementvariable R′ for the arterial oxygenation. For each of the emitters 31Eand 32E, three wavelengths are defined. Initially, two measurementwavelengths w0=940 nm and w2=660 nm are selected. Using equation (4) thethird wavelengths w1 is about 788 nm. Wavelength w1=805 nm is chosenbecause it is close to the calculated third wavelength and isadditionally at an isobestic point of the blood absorption spectrum. Thenext step is to determine the resulting light attenuation LA for each ofthe three wavelengths w0, w1 and w3:

LAw1=LA(A3w1)+LA(A2w1)−LA(A1w1)−LA(A4w1)   eq. (5)

LAw2=LA(A3w2)+LA(A2w2)−LA(A1w2)−LA(A4w2)   eq. (6)

LAw3=LA(A3w3)+LA(A2w3)−LA(A1w3)−LA(A4w3)   eq. (7)

where LA(Axwy) is the logarithm of received light intensity in thedetector related to light arrow Ax at wavelength wy. The suffix x forlight arrows Ax represents the number of the selected light arrow and ythe suffix for the selected wavelength. Instead of the logarithm oflight intensities, light intensity itself can be used in eq. (5)-(7) and“+” is replaced by “*” and “−” is replaced by “/”.

In the next step, Rw2,w1 and Rw1,w0 are calculated according to equation(1). As a result Fr can be determined using equation (2) with Q as acorrection factor which can be dependant on Rw2,w1 or Rw1,w0. Themeasured arterial oxygenation which is dependant on R′ has minimizedinfluence of scattering, blood content or other optical absorbingconstituents in tissue.

The quotient in (8) which is part of (2) delivers a measurement variableRv′:

$\begin{matrix}{{Rv}^{\prime} = \frac{{LAw}\; 2*{LAw}\; 0}{{LAw}\; 1*{LAw}\; 1}} & {{eq}.\mspace{11mu} (8)}\end{matrix}$

Rv′ is a measure of optical absorption of tissue with decreasedinfluence of scattering. Therefore it can be used as a signal for mixedvenous oxygenation SvO2.

A mathematically identical form of (2) is:

$\begin{matrix}{R^{\prime} = \frac{{w\; 2},{{w\; 0*{Rv}^{\prime}} + Q}}{{{Rw}\; 1},{w\; 0*{Rw}\; 1},{w\; 0}}} & {{eq}.\mspace{11mu} (9)}\end{matrix}$

According to eq. (9) the following equation can also be used todetermine a measurement variable R1′ for SaO2:

$\begin{matrix}{{R\; 1^{\prime}} = \frac{{{Rw}\; 2},{w\; 0*{f\left( {1,{Rv}^{\prime},Q} \right)}}}{{{Rw}\; 1},{w\; 0*{Rw}\; 1},{w\; 0}}} & {{eq}.\mspace{11mu} (10)}\end{matrix}$

where f is an empirical function of optical tissue parameters withvariables defined above.

An empirical calibration which reduces influence of absorption andscattering of tissue on the measured variables with the variables LAw1,LAw2, LAw3, Rw1,w2 and Rw2,w3 for the whole saturation range of blood iscomplex. An pure empirical calibration based on these parametersadditionally for different application sites is probably impossible. Theproposed model-based method reduces complexity of calibration. SaO2 canbe determined with improved accuracy being only dependent on R′.

It is also possible to use this method for other light absorbingconstituents of blood like carboxyhemoglobin methemoglobin, bilirubin orglucose dissolved in blood. Light wavelength in the range from 600nm-1000 nm can be used for carboxyhemoglobin and methemoglobin. Glucoseshows an absorption peek dissolved in blood at 1100 nm and bilirubin inthe lower wavelengths range from 300 nm-800 nm. For every additionalconstituent an additional wavelengths has to be chosen. That means thatto measure SaO2 and methemoglobin at a time, four wavelength have to beselected and two different measurement variables R′1 and R′2 accordingequation (9) have to be defined. Accordingly, the resulting output forSaO2 is dependent on R′1 and methemoglobin on R′2.

As a result sensor 31S is able to measure arterial and mixed venousoxygenation and other blood constituents at a time with reducedinfluence of measurement errors due to scattering and absorption oftissue.

EXAMPLE 2

In FIG. 4 finger clip sensor 54 is shown with the two emitters 31E, 32Eand the two detectors 31D and 32D. The benefit of the finger clip sensoris that it is easy to apply. Equivalent to sensor 31S in FIG. 3, fourrepresentative light paths between the two emitters and the twodetectors are possible so that all calculations according example 1 canbe performed in order to calculate the output variables R′ and Rv′ as ameasure for mixed venous and arterial oxygenation in the finger 48. Thecorresponding calculations can also be performed using sensor of FIG. 9.The difference here is the alternative form of detectors 35D and 36D,which are able to increase detected light intensity due to an enlarged,concentric detector area.

EXAMPLE 3

FIG. 5 shows a multidimensional calibration of SAO2 vs. R1 and R2. R1and R2 can be calculated according (1) by selecting two wavelengthspairs where for the first wavelengths pair the wavelengths wm1=660 nmand wm2=910 nm is chosen and for the second wavelengths pair wm3=810 nmand wm2=910 nm. The second wavelengths pair is less sensitive towardsarterial oxygenation and is used to compensate errors due to opticaltissue parameter variations. In order to guarantee that themultidimensional calibration delivers improved precision in presence ofvarying tissue parameters, it is important to select exactly thecorrespondent calibration which is specified for a distinct wavelengthsset and a distinct detector emitter distance. Therefore additionalinformation has to be coded to the selected sensor. The tissue oximeterdevice can read out this information and use the appropriatecalibration. The coding of information can be achieved for example by aresistor implemented in the LED drive line of the sensor (see FIG. 17:248, 238). A grounded shield plane 233 between an isolating layer 239and the light sensing elements 31D an 32D is useful to minimize theelectrical interference and noise. The isolating layer can also be usedto decouple forces e.g. for wrist worn devices 220 with and integratedsensor interface to control the forces of sensor interface on tissuewhich can have influences on sensor precision. Also an elastic wristband 221 can help to decrease this influence.

A variant of a multidimensional calibration (FIG. 5) can be achieved bycalculating R1 according to equation (2) and R2 according to equation(8). This minimizes the error of displayed arterial oxygenation SaO2 dueto varying optical tissue absorption.

EXAMPLE 4

In FIG. 7 a fetal pulse oximetry sensor 74 is shown, which punctures theskin on the head of the fetus with a spiral needle 76. The bottom viewof FIG. 8 shows sensor 74 with 4 emitters 31E, 32E, 33E, 34E and fourdetectors 31D, 32D, 33D, 34D. Apparently, more than four different lightpaths per selected wavelength between emitters and detectors (is) arepossible. This additional information is used to calculate a whole setof resulting light attenuations Lax. For the different light paths it isalso possible to compute a set of measurement variables Rx. Generating aweighted mean value (weight can depend on the noise of the relatedmeasurement signals) LAm and Rm of the variables LAx and Rx helps toreduce errors due to tissue inhomogenities. To achieve a stable measurefor the optical tissue parameters, which are not influenced by locallyvarying tissue compositions, is important to minimize errors toprecisely determine the inputs of model-based parameters.

EXAMPLE 5

A brain oximeter is shown in FIG. 13A which is positioned on the rightside of the forehead of a patient. The cross section of the brainillustrates how four light paths travel through tissue from emitters31E, 32E to the detectors 31D and 32D, representative for onewavelength. A resulting light attenuation LA can be achieved for eachwavelength by adding light attenuations of A32 and A22 and subtractingtherefrom the light attentions which are related to A42 and A12. Theresulting light attenuation LA is then independent on dirt on emittersor detectors or on degeneration of those parts, which is an importantfeature since those sensors can be reused. Three wavelengths are chosenfor each of the two emitters 31E and 32E of the sensor in FIG. 13A ofthe brain oximeter: wb1=660 nm, wb2=740 nm and wb3=810 nm.

The ratio Rvb of the resulting light attentions LAwb2 and LAwb3 is usedas a measure for the mixed venous oxygenation. The resulting lightattenuation at wavelength wb3=810 nm can be used to eliminate thedependency of blood content in tissue of Rvb with a multidimensionalcalibration of SvO2 vs. Rvb and LAwb3.

A preferred emitter-detector distance between emitter 32E and detector31D is greater than 2 cm. In order to contrast brain tissue andoverlaying tissues one long light path should have an emitter detectordistance of about 4 cm and a shorter one with an emitter detectordistance of about 2 cm to distinguish the overlaying structures. Therelation of noise on the signal and signal portion related mainly tobrain is a good compromise for this application. The longer the distancethe emitter detector distance is, the deeper is the penetration depthinto the brain. In order to achieve maximum penetration depth at aminimum of sensor outline, the distance between an emitter and adetector should be the maximum distance between all emitters anddetectors. FIG. 14 shows an example where within the sensor, the twodetectors have the maximum distance and the detector and emitterelements are grouped symmetrically with regard to the center of thesensor. The resulting maximum penetration depth of light of A31, A21 ishere less than maximum penetration depth of light of A32 of the sensorwhich illustrated in FIG. 13A because the maximum emitter detectordistance is also less compared to sensor in FIG. 13A at the same totaloutline of the sensors. Positioning emitters and detectorsasymmetrically is therefore the best choice to achieve oxygenationmeasurements in deep layers of tissue. In FIG. 13B emitter 31E ispositioned close to emitter 32E. Detector 32D is positioned betweendetector 31D and emitter 32E. Adding the light attenuation A32 and A22and subtracting A12 and A42 results in a signal where most of the brainoverlaying structures can be contrasted versus brain tissue and whereoxygenation signals can be calculated which are originated for more than80% from brain tissue and not overlaying structures.

FIG. 12 shows a bottom view of a brain oximetry sensor, in which emitter31E and detectors 31D and 32D are positioned in a triangle. The lightpaths between emitter 31E and 31D and between 31E and 32D using thewavelengths wb1=660 nm and wb3=810 nm are determined to evaluate themeasurement variables Rp1 and Rp2 which are calculated according toequation (1). The mean value of Rp1 and Rp 2 is used as the output valuefor the arterial oxygenation SaO2. Alternatively, as shown in FIG. 12A,the emitters 31E and 32E can be positioned where detectors 31D and 32Dare located and detectors 31D and 32D are placed at the location ofemitter 31E and 32E in FIG. 12. In FIG. 12B the detector 31D1 ispositioned in between of the emitters 31E and 123E. Adding andsubtracting light attenuations of the related light paths between 31D1and 31E and the light path between 31D1 and 123E minimizes theinfluences of shallow tissue layers as they cancel out. FIG. 12C shows asensor analogous to FIG. 12B. The difference here is that detector 31D1is replaced by detector 31D1 and 31D2. Adding the light intensities ofthis two detectors before calculating the light attenuation thereofresults that the related attenuation of detector 31D1 and 31D1 forfurther calculation can be handled like a single detector. According tothis emitters 31E and 123D can be positioned closer by avoiding lightshunting between detectors 31D1, 31D2 and emitters 31E and 123E. FIG.12D shows an alternative position detectors 31D1 and 31D2. In order tomonitor the oxygenation balance of brain for both hemispheres a sensoron the right and left side can be used according to the illustration inFIG. 16 with sensor interfaces 214, 215.

EXAMPLE 6

Referring to Example 5, a brain oximetry sensor was described which isable to determine arterial and mixed venous oxygenation of tissue. Thesetwo parameters can be used to calculate the oxygen extraction of tissue.A measure therefore can be the difference of arterial and mixed venousoxygenation. Oxygen extraction reflects how well tissue is supplied withoxygen, and can additionally be used to calculate the cardiac output orthe trend of the cardiac output CaOut non-invasively. FIG. 15 shows apatient being supplied with air via an intubation tube 210. The oxygenconsumption or CO2 generation is determined within an anesthesia machine204. Brain oximetry sensor 32S is connected to SaO2 and SvO2 displaydevice 206. The information of device 204 and device 206 is evaluated ina cardiac output monitor 202 in the following or similar manner:

$\begin{matrix}{{CaOut} = \frac{\left( {{oxygen}\mspace{14mu} {consumption}\mspace{14mu} {per}\mspace{14mu} {time}} \right)}{{{SaO}\; 2} - {{SvO}\; 2}}} & {{eq}.\mspace{11mu} (11)}\end{matrix}$

EXAMPLE 7

Knowledge of oxygenation of tissue of parts of the body is of highinterest for sports activity monitoring, The oxygenation the muscles ofthe upper leg or upper arm can reflect the training level for differentactivities of sport. FIG. 16 shows an athlete wearing various sensorswhich are connected by a line or wirelessly with a wrist-worn-display220. A sports activity sensor can have the same topology as the abovementioned brain sensor of FIG. 12. Emitter-detector distances howevervary, depending on desired tissue monitoring depth. Preferredwavelengths to monitor the mixed venous oxygenation are ws1:=700 nm,ws2=805 nm and ws3=870 nm. A resulting light attenuation LA iscalculated for each wavelength: LWws1, LAws2 and LAws3 with ws1, ws2 andws3 as index for the selected wavelengths. A measurement variable forthe mixed venous oxygenation Rvs is obtained in the following or similarmanner:

$\begin{matrix}{{Rvs} = \frac{{{LAws}\; 1} - {{LAws}\; 2}}{{{LAws}\; 2} - {{LAws}\; 3}}} & {{eq}.\mspace{11mu} (12)}\end{matrix}$

Less influence of light scattering and absorption of tissue can beachieved for the determination of mixed venous oxygenation in this way.

A further improvement for better measurement precision can be achievedby generating an output value for the mixed venous oxygenation which isdependant on a multidimensional calibration of SvO2 vs. Rvs and Rv.

Although the description above contains many specificities, these shouldnot be constructed as limiting the scope of the invention but as merelyproviding illustrations of some of the presently preferred embodimentsof this invention. For example the shape of the emitters can berectangular, emitters can include LEDs, detectors photodiodes; the shapeof the brain sensor can be round; the proposed methods to calculatearterial and mixed venous oxygenation of tissue can be combined indifferent combinations, signals can be processed by Kalman filters inorder to reduce influence of noise caused by motion or other unwantedsources, etc.

The present subject matter includes various examples, including thefollowing:

Example 1 includes an apparatus for measuring tissue oxygenation of apatient comprising:

a sensor interface adapted to be coupled to a patient tissue site andincluding at least one light emitter emitting light into tissue and atleast one detector detecting light passing through tissue from said atleast one emitter;a processor for determining light attenuations LAwsj dependant on lightdetected at a selected wavelength, wsj;a coupling device for coupling said sensor interface at said tissuesite;a data processor for generating a signal representative of tissueoxygenation based on said determined light attenuations; anda display device displaying a tissue oxygenation level.

Example 2 includes the apparatus of example 1 wherein said dataprocessor includes means for generating a signal representative oftissue oxygenation and provides arterial oxygenation information basedon pulsating changes of light attenuations.

Example 3 includes the apparatus of example 2 wherein said sensorcoupling device is an arm band.

Example 4 includes the apparatus of example 3 wherein said armband is awrist band.

Example 5 includes the apparatus of example 3 comprising: elastic meansfor controlling a force applied to tissue through the sensor interface.

Example 6 includes an apparatus for measuring tissue oxygenationcomprising:

a sensor interface including at least two emitters which emits lightinto tissue with at least two wavelengths, and at least one detector toreceive light passing through said tissue;a storage device for retaining information of sensor variation withinsaid sensor interface; anda processor for determining tissue oxygenation using said sensorvariation information of said sensor interface.

Example 7 includes the apparatus according to example 6 wherein a lightemission intensity of at least one of said emitters and a wavelength ofat least one of said emitters is compensated for by said means forcalculating.

Example 8 includes the apparatus according to example 7 wherein braintissue oxygenation is determined using said sensor interface with atleast one emitter/detector distance being greater than 3 cm and saidsensor interface being provided at one side of a forehead, saidapparatus measuring the oxygenation of one brain hemisphere.

Example 9 includes the apparatus according to example 8 wherein at leastone emitter detector distance is about 1 cm long and a related path canbe used to determine a light attenuation or additionally arterialoxygenation by evaluating a pulsatile part of detected light.

Example 10 includes an apparatus for measuring tissue oxygenationcomprising:

a sensor adapted to be coupled to a forehead tissue including at leasttwo light emitters placed apart from each other on said sensor with atleast two different wavelengths for each emitter where each emitter hasapproximately the same wavelengths which emit light into said tissue andat least one detector for detecting light having passed through saidtissue, whereby a distance of one of said emitters and one of said atleast one detector is chosen so that a light path penetrates through thetissue and whereby a distance between at least one emitter-detector pairis more than 20 millimeters;means for calculating at least two signals which depend on detectedlight for selected wavelengths wsj for said at least one detector andsaid at least two emitters, wherein said at least two signals arecalculated by adding or subtracting light attenuations;means for calculating attenuation corresponding to In(intensity ofsteady state light received at the detector) for at least two possiblelight paths between said at least two light emitters and said at leastone detector; andmeans for generating an output representative of tissue oxygenationbased on the at least said two signals.

Example 11 includes the apparatus of example 10 using at least twoemitters and at least two detectors whereby for at least two of saidwavelengths for each of the wavelengths the corresponding lightattenuations for two light paths are added and the corresponding lightattenuation for two further light paths are subtracted to generate ameasure for said at least two signals.

Example 12 includes the apparatus of example 11 wherein said sensorincludes at least one emitter detector distance of at least 4 cm and asecond emitter detector distance of at least 1.5 cm.

Example 13 includes the apparatus of example 10 wherein said sensorincludes at least one emitter detector distance of at least 4 cm and asecond emitter detector distance of at least 1.5 cm.

Example 14 includes the apparatus of example 12 wherein at least 65% ofa generated oxygenation signal is originated by brain tissue by addingand subtracting light paths through forehead tissue and brain tissue,

Example 15 includes the apparatus of example 13 wherein anemitter-detector distance of the sensor placed on one side of theforehead to monitor a brain hemisphere is less than 20 mm long.

Example 16 includes the apparatus of example 13 having a means tocalculate a measure for arterial oxygenation using a light signalrelated to an emitter-detector pair separated by a distance of no morethan 20 mm.

Although the present invention and its advantages have been described indetail, it should be understood that various changes, substitutions andalterations can be made herein without departing from the spirit andscope of the invention as defined by the appended claims. Moreover, thescope of the present application is not intended to be limited to theparticular embodiments of the process, machine, manufacture, compositionof matter, means, methods and steps described in the specification. Asone of ordinary skill in the art will readily appreciate from thedisclosure of the present invention, processes, machines, manufacture,compositions of matter, means, methods; or steps, presently existing orlater to be developed that perform substantially the same function orachieve substantially the same result as the corresponding embodimentsdescribed herein may be utilized according to the present invention.Accordingly, the appended claims are intended to include within theirscope such processes, machines, manufacture, compositions of matter,means, methods; or steps.

1. Apparatus and sensor for measuring constituents of blood in tissue invivo with a sensor connected to said apparatus determining lightattenuation at a combination of light emitters and detectors comprisingthe following means: a light emitter and at least two detectors, saidlight emitter including at least three wavelengths, wherein a peakspectrum of one of said at least three wavelengths is about thegeometric mean value of the two other of said three wavelengths; meansfor calculating at least two values of differential attenuation vs. timeRw1, w2, Rw2,w3 with w1, w2,w3 representing the selected wavelengths;means for eliminating influences on calibration by subtracting andadding measured light attenuations to generate a signal; and means forgenerating a resulting output signal for a constituent of blood in vivodepending on said signal; wherein said means for generating a resultingoutput minimizes the error on said resulting output.
 2. The apparatus ofclaim 1, wherein said constituent is selected from the group consistingof carboxyhemoglobin, methemoglobin, glucose in blood, Hb, SvO2, SaO2and bilirubin.
 3. An apparatus for measuring constituents of blood intissue, including a sensor with a combination of two light emitters andtwo light detectors, said apparatus comprising: means for emitting alight wavelength combination including at least two wavelengths with atleast one emitter, wherein the peak spectrum of one of said at leastthree wavelengths is about the geometric mean value of the two others ofsaid three wavelengths to generate a first output signal; means forcalculating differential attenuation vs. time Rw1, w2, Rw2, w3; meansfor eliminating influences on calibration by an operation whichcorresponds to subtracting and adding measured light attenuations togenerate an output signal for optical properties; means for encodinginformation about the sensor for compensating influences of varyingoptical tissue properties related to said sensor interface; means forgenerating a resulting output signal for at least one of saidconstituents of blood in vivo depending on said means measured on theforehead or back or chest or arm of the body; and means for generatingan output signal for cardiac output depending on said bloodconstituents, wherein said means for generating the resulting outputsignal for at least one of said constituents minimizes the error on saidresulting output.